tbuckley/cabot-search huggingface dataset:
Preclinical evaluation of KH631, a novel rAAV8 gene therapy product for neovascular age-related macular degeneration
Authors: Xiao Ke, Hao Jiang, Qingwei Li, Shuang Luo, Yingfei Qin, Jing Li, Qing Xie, Qiang Zheng
Journal: Molecular Therapy (2023)

The upregulation of vascular endothelial growth factor (VEGF) is strongly associated with the development of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (nAMD). Currently, the standard treatment for nAMD involves frequent intravitreal injections of anti-VEGF agents, which inhibit the growth of new blood vessels and prevent leakage. However, this treatment regimen places a significant burden on patients, their families, and healthcare providers due to the need for repeated visits to the clinic for injections. Gene therapy, which enables the sustained expression of anti-VEGF proteins after a single injection, can dramatically reduce the treatment burden. KH631 is a recombinant adeno-associated virus 8 vector that encodes a human VEGF receptor fusion protein, and it is being developed as a long-term treatment for nAMD. In preclinical studies using non-human primates, subretinal administration of KH631 at a low dose of 3 × 10
The cognitive (lateral) hypothalamus
Authors: Melissa J. Sharpe
Journal: Trends in Cognitive Sciences (2023)

Despite the physiological complexity of the hypothalamus, its role is typically restricted to initiation or cessation of innate behaviors. For example, theories of lateral hypothalamus argue that it is a switch to turn feeding 'on' and 'off' as dictated by higher-order structures that render when feeding is appropriate. However, recent data demonstrate that the lateral hypothalamus is critical for learning about food-related cues. Furthermore, the lateral hypothalamus opposes learning about information that is neutral or distal to food. This reveals the lateral hypothalamus as a unique arbitrator of learning capable of shifting behavior toward or away from important events. This has relevance for disorders characterized by changes in this balance, including addiction and schizophrenia. Generally, this suggests that hypothalamic function is more complex than increasing or decreasing innate behaviors.
Uncovering the Changing Treatment Landscape for Low-risk Prostate Cancer in the USA from 2010 to 2020: Insights from the National Cancer Data Base
Authors: Edoardo Beatrici, Muhieddine Labban, Benjamin V. Stone, Dejan K. Filipas, Leonardo O. Reis, Giovanni Lughezzani, Nicolò M. Buffi, Adam S. Kibel, Alexander P. Cole, Quoc-Dien Trinh
Journal: European Urology (2023)
Associations between rheumatoid arthritis and skin cancer: A bidirectional two-sample Mendelian randomization study
Authors: Nianzhou Yu, Haoxiang Qi, Yeye Guo, Lisha Wu, Juan Su, Kai Huang, Yixin Li, Zixi Jiang, Shuang Zhao, Xiang Chen
Journal: Journal of the American Academy of Dermatology (2023)
Middle meatus microbiome in patients with eosinophilic chronic rhinosinusitis in a Japanese population
Authors: Masanori Kidoguchi, Yoshimasa Imoto, Emiko Noguchi, Takako Nakamura, Wataru Morii, Naoto Adachi, Rieko Ii, Keisuke Koyama, Satoshi Aoki, Keisuke Miyashita, Yu Hosokawa, Kazuhiro Omura, Yasuhiro Tanaka, Kaori Tanaka, Yukio Hida, Takahiro Ninomiya, Yukinori Kato, Masafumi Sakashita, Tetsuji Takabayashi, Shigeharu Fujieda
Journal: Journal of Allergy and Clinical Immunology (2023)
Ex Vivo Evaluation of Combination Immunotherapy Using Tumor‐Microenvironment‐on‐Chip
Authors: Hsuan‐Yu Mu, Chiao‐Min Lin, Li‐An Chu, Ya‐Hui Lin, Ji Li, Chao‐Yu Liu, Hsi‐Chien Huang, Sheng‐Liang Cheng, Tsung‐Ying Lee, Hsin Mei Lee, Hsin‐Min Chen, Yun‐Jen Tsai, Yunching Chen, Jen‐Huang Huang
Journal: Advanced Healthcare Materials (2023)

Abstract Combination immunotherapy has emerged as a promising strategy to address the challenges associated with immune checkpoint inhibitor (ICI) therapy in breast cancer. The efficacy of combination immunotherapy hinges upon the intricate and dynamic nature of the tumor microenvironment (TME), characterized by cellular heterogeneity and molecular gradients. However, current methodologies for drug screening often fail to accurately replicate these complex conditions, resulting in limited predictive capacity for treatment outcomes. Here, a tumor‐microenvironment‐on‐chip (TMoC), integrating a circulation system and ex vivo tissue culture with physiological oxygen and nutrient gradients, is described. This platform enables spatial infiltration of cytotoxic CD8 + T cells and their targeted attack on the tumor, while preserving the high complexity and heterogeneity of the TME. The TMoC is employed to assess the synergistic effect of five targeted therapy drugs and five chemotherapy drugs in combination with immunotherapy, demonstrating strong concordance between chip and animal model responses. The TMoC holds significant potential for advancing drug development and guiding clinical decision‐making, as it offers valuable insights into the complex dynamics of the TME.
Mechanisms of weight loss-induced remission in people with prediabetes: a post-hoc analysis of the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS)
Authors: Arvid Sandforth, Reiner Jumpertz von Schwartzenberg, Elsa Vazquez Arreola, Robert L Hanson, Gencer Sancar, Sarah Katzenstein, Karl Lange, Hubert Preißl, Simon I Dreher, Cora Weigert, Robert Wagner, Kostantinos Kantartzis, Jürgen Machann, Fritz Schick, Rainer Lehmann, Andreas Peter, Nikoletta Katsouli, Vasilis Ntziachristos, Corinna Dannecker, Louise Fritsche, Nikolaos Perakakis, Martin Heni, Peter Paul Nawroth, Stefan Kopf, Andreas F H Pfeiffer, Stefan Kabisch, Michael Stumvoll, Peter E H Schwarz, Hans Hauner, Andreas Lechner, Jochen Seissler, Iryna Yurchenko, Andrea Icks, Michele Solimena, Hans-Ulrich Häring, Julia Szendroedi, Annette Schürmann, Martin Hrabé de Angelis, Matthias Blüher, Michael Roden, Stefan R Bornstein, Norbert Stefan, Andreas Fritsche, Andreas L Birkenfeld
Journal: The Lancet Diabetes & Endocrinology (2023)
A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance
Authors: Lei Sun, Arabella H. Wan, Shijia Yan, Ruonian Liu, Jiarui Li, Zhuolong Zhou, Ruirui Wu, Dongshi Chen, Xianzhang Bu, Jingxing Ou, Kai Li, Xiongbin Lu, Guohui Wan, Zunfu Ke
Journal: Acta Pharmaceutica Sinica B (2023)

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.
Early maladaptive schemas and behavioural addictions: A systematic literature review
Authors: Claudio Vieira, Daria J. Kuss, Mark D. Griffiths
Journal: Clinical Psychology Review (2023)

As observed in other mental health difficulties, behavioural addiction is a complex construct with several potential predisposing factors, which include biological factors (e.g., genetic predispositions), psychological factors (e.g., personality traits), and social factors (e.g., family, and social history). One factor that may play a significant role in both developing and perpetuating behavioural addiction is the activation of early maladaptive schemas (EMSs). The aim of the present review was to synthesize the evidence concerning the relationship between behavioural addiction and EMSs. A comprehensive literature search using keywords and subject headings was performed with three electronic databases, resulting in 20 studies that met the inclusion criteria. In relation to specific behavioural addiction, the 20 studies examined: binge-eating/food addiction (n = 6), sexual addiction/compulsive sexual behaviours (n = 3), multiple addictive behaviours (n = 2), internet addiction (n = 2), smartphone addiction (n = 2), social networking/Facebook addiction (n = 2), exercise dependence (n = 1), gambling (n = 1), and videogame addiction (n = 1). The patterns of association between EMS and behavioural addiction were examined in both clinical and non-clinical population. The 'Disconnection and Rejection' domain was the most strongly related schema domain across all addictive behaviours, followed by 'Impaired Limits'. The present review suggests a positive relationship between schema activation and several addictive behaviours, including addictions to gambling, gaming, social media use sex, exercise, and food. The clinical implications of the findings are discussed, but further research is needed to inform treatment plans and interventions for those who struggle with behavioural addictions.
Ethical Guidance for Physicians and Health Care Institutions on Grateful Patient Fundraising: A Position Paper From the American College of Physicians
Authors: Lois Snyder Sulmasy, T. Brian Callister, Isaac O. Opole, Noel N. Deep, Isaac O. Opole, T. Brian Callister, Sue S. Bornstein, Eduardo Bruera, Jan K. Carney, Angelique N. Collamer, Kari L. Esbensen, Olivia I. Fuson, Amy K. Holbrook, Diana Jung, Ryan D. Mire, Kenneth M. Prager, Erik A. Wallace
Journal: Annals of Internal Medicine (2023)

Physician solicitation of charitable contributions from patients-also known among other things as grateful patient fundraising-raises significant ethical concerns. These include pressure on patients to donate and the effects of this on the patient-physician relationship, potential expectations of donor patients for treatment that is not indicated or preferential care, justice and fairness issues, disclosure and use of confidential patient information for nontreatment purposes, and conflicts of interest. The patient-physician relationship and knowledge of the patient's medical history, clinical status, personal information, and financial circumstances are some of the reasons development and administrative officials might see physicians as strong potential fundraisers. But those are among the reasons grateful patient fundraising is ethically problematic. This American College of Physicians position paper explores these issues and offers guidance.
Once-Weekly Insulin Icodec With Dosing Guide App Versus Once-Daily Basal Insulin Analogues in Insulin-Naive Type 2 Diabetes (ONWARDS 5)
Authors: Harpreet S. Bajaj, Jens Aberle, Melanie Davies, Anders Meller Donatsky, Marie Frederiksen, Dilek G. Yavuz, Amoolya Gowda, Ildiko Lingvay, Bruce Bode
Journal: Annals of Internal Medicine (2023)

Inadequate dose titration and poor adherence to basal insulin can lead to suboptimal glycemic control in persons with type 2 diabetes (T2D). Once-weekly insulin icodec (icodec) is a basal insulin analogue that is in development and is aimed at reducing treatment burden.
Blood Pressure Level in Late Adolescence and Risk for Cardiovascular Events
Authors: Helene Rietz, Johanna Pennlert, Peter Nordström, Mattias Brunström
Journal: Annals of Internal Medicine (2023)

Not enough is known about the association between blood pressure (BP) in adolescence and future cardiovascular events.To measure this association using the 2017 American College of Cardiology/American Heart Association guidelines for classifying BP elevation.Cohort study.Sweden.Males in late adolescence who were conscripted into the military from 1969 to 1997.Baseline BP was measured at conscription. The primary outcome was a composite of cardiovascular death or first hospitalization for myocardial infarction, heart failure, ischemic stroke, or intracerebral hemorrhage.The study included 1 366 519 males with a mean age of 18.3 years. The baseline BP was classified as elevated (120 to 129/<80 mm Hg) for 28.8% of participants and hypertensive (≥130/80 mm Hg) for 53.7%. During a median follow-up of 35.9 years, 79 644 had a primary outcome. The adjusted hazard ratio was 1.10 for elevated BP (95% CI, 1.07 to 1.13), 1.15 for stage 1 isolated systolic hypertension (ISH) (CI, 1.11 to 1.18), 1.23 for stage 1 isolated diastolic hypertension (IDH) (CI, 1.18 to 1.28), 1.32 for stage 1 systolic-diastolic hypertension (SDH) (CI, 1.27 to 1.37), 1.31 for stage 2 ISH (CI, 1.28 to 1.35), 1.55 for stage 2 IDH (CI, 1.42 to 1.69), and 1.71 for stage 2 SDH (CI, 1.58 to 1.84). The cumulative risk for cardiovascular events also increased gradually across BP stages, ranging from 14.7% for normal BP to 24.3% for stage 2 SDH at age 68 years.This was an observational study of Swedish men.Increasing BP levels in late adolescence are associated with gradually increasing risks for major cardiovascular events, beginning at a BP level of 120/80 mm Hg.Västerbotten County Council, Swedish Society for Medical Research, and Heart Foundation of Northern Sweden.
Annals Graphic Medicine - A Series of Realizations as a First-Year Medical Student
Authors: Oscar Li
Journal: Annals of Internal Medicine (2023)

Web Exclusives26 September 2023Annals Graphic Medicine - A Series of Realizations as a First-Year Medical StudentFREEOscar Li, BSOscar Li, BSJohns Hopkins University School of Medicine, Baltimore, Maryland (O.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G22-0059 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Author, Article, and Disclosure InformationAuthors: Oscar Li, BSAffiliations: Johns Hopkins University School of Medicine, Baltimore, Maryland (O.L.)Disclosures: The author has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G22-0059.Author/Illustrator Information: Oscar Li, BS, is an award-winning filmmaker and third-year medical student at the Johns Hopkins University School of Medicine (e-mail, onlioscarli@gmail.com; website, www.onlyoscarli.com).This article was published at Annals.org on 26 September 2023. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Current IssueOctober 2023Volume 176, Issue 10 ePublished: 26 September 2023 Issue Published: October 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Circulating hormones in biopsy-proven steatotic liver disease and steatohepatitis: A Multicenter Observational Study
Authors: Laura Valenzuela-Vallejo, Pavlina Chrysafi, Matina Kouvari, Valentina Guatibonza-Garcia, Sophia C. Mylonakis, Angeliki Katsarou, Ornella Verrastro, Georgios Markakis, Mohammed Eslam, Georgios Papatheodoridis, Geltrude Mingrone, Jacob George, Christos S. Mantzoros
Journal: Metabolism (2023)
Aging-disturbed FUS phase transition impairs hematopoietic stem cells by altering chromatin structure
Authors: Baixue Tang, Xinming Wang, Hanqing He, Ruiqing Chen, Guofeng Qiao, Yang Yang, Zihan Xu, Longteng Wang, Qiongye Dong, Jia Yu, Michael Q. Zhang, Minglei Shi, Jianwei Wang
Journal: Blood (2023)
Elevated serum TARC levels precede classic Hodgkin lymphoma diagnosis by several years
Authors: Arjan Diepstra, Ilja M. Nolte, Anke van den Berg, Larry I. Magpantay, Otoniel Martínez-Maza, Lynn I. Levin
Journal: Blood (2023)

Tumor cells in classic Hodgkin lymphoma produce high quantities of the thymus- and activation-related chemokine (TARC). We measured TARC levels in prediagnostic serum samples and found strikingly increased values in the vast majority of patients, as early as 6 years before diagnosis.
Impact of Type 2 Diabetes on the Outcomes of Solid Organ Transplantations in the U.S.: Data From a National Registry
Authors: Maria Stepanova, Ameeta Kumar, Pamela Brandt, Nagashree Gundurao, Kenneth Cusi, Saleh Al Qahtani, Zobair M. Younossi
Journal: Diabetes Care (2023)

OBJECTIVE Type 2 diabetes (T2D) is a major driver of chronic diseases around the globe. The aim was to assess the impact of T2D on the outcomes of solid organ transplantations. RESEARCH DESIGN AND METHODS We used the Scientific Registry of Transplant Recipients from 2006 to 2021 to collect data for all patients age ≥18 years who received a lung, heart, liver, or kidney transplant in the U.S. RESULTS We included 462,692 solid organ transplant recipients: 31,503 lung, 38,004 heart, 106,639 liver, and 286,440 kidney transplantations. The prevalence of pretransplantation T2D was 15% in lung, 26% in heart, 25% in liver, and 30% in kidney transplant recipients, increasing over time. Posttransplantation mortality was significantly higher among transplant recipients with T2D versus those without T2D (lung 32.1% vs. 29.3% [3 years], 46.4% vs. 42.6% [5 years]; P &amp;lt; 0.01; heart 11.2% vs. 9.1% [1 year], 24.4% vs. 20.6% [5 years]; P &amp;lt; 0.0001; liver 10.6% vs. 8.9% [1 year], 26.2% vs. 22.0% [5 years]; P &amp;lt; 0.0001; kidney 5.3% vs. 2.5% [1 year], 20.8% vs. 10.1% [5 years]; P &amp;lt; 0.0001). Independent association of pretransplantation T2D with higher posttransplantation mortality was significant after adjustment for clinicodemographic confounders (adjusted hazard ratio in lung transplant recipients 1.08 [95% CI 1.03–1.13]; heart 1.26 [1.20–1.32]; liver 1.25 [1.21–1.28]; kidney 1.65 [1.62–1.68]; P &amp;lt; 0.01). CONCLUSIONS The prevalence of T2D in solid organ transplantation candidates is increasing. In all solid organ transplantations, pretransplantation T2D was independently associated with higher posttransplantation mortality, most profoundly in kidney transplantations.
Nine-Week Versus One-Year Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: 10-Year Update of the ShortHER Phase III Randomized Trial
Authors: PierFranco Conte, Giancarlo Bisagni, Federico Piacentini, Samanta Sarti, Santino Minichillo, Elisa Anselmi, Michele Aieta, Vittorio Gebbia, Alessio Schirone, Antonino Musolino, Ornella Garrone, Alessandra Beano, Anita Rimanti, Francesco Giotta, Anna Turletti, Federica Miglietta, Maria Vittoria Dieci, Roberto Vicini, Sara Balduzzi, Robert D'Amico, Valentina Guarneri
Journal: Journal of Clinical Oncology (2023)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We present the final analysis of the phase III noninferiority, randomized ShortHER trial comparing 9 weeks versus 1 year of adjuvant trastuzumab with chemotherapy in patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC). Women with HER2+ BC were randomly assigned to anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or 9-week trastuzumab (arm B, short). Here, we report the second coprimary end point overall survival (OS), updated disease-free survival (DFS), and outcomes according to hormone receptor status, age, and nodal status. At a median follow-up of 9 years, 10-year DFS is 77% versus 78% in the long versus short arm, respectively. Ten-year OS is 89% versus 88% in the long versus short arm, respectively. 10-year DFS rates in the long versus short arm according to nodal status are N0 81% versus 85%; N1-3 77% versus 79%; and N4+ 63% versus 53%. Ten-year OS rates in long versus short arm according to nodal status are N0 89% versus 95%%; N1-3 92% versus 89%; and N4+ 84% versus 64%. The updated analysis of the ShortHER trial shows that 1-year trastuzumab is the standard treatment for patients with HER2+ early BC as noninferiority cannot be claimed. However, numerically, the differences for the patients at low or intermediate risk (N0/N1-3) is negligible, while patients with N4+ have a clear benefit with 1-year trastuzumab.
Prophylactic Radiation Therapy Versus Standard of Care for Patients With High-Risk Asymptomatic Bone Metastases: A Multicenter, Randomized Phase II Clinical Trial
Authors: Erin F. Gillespie, Joanna C. Yang, Noah J. Mathis, Catherine B. Marine, Charlie White, Zhigang Zhang, Christopher A. Barker, Rupesh Kotecha, Alyson McIntosh, Max Vaynrub, Meredith K. Bartelstein, Aaron Mitchell, David M. Guttmann, Divya Yerramilli, Daniel S. Higginson, Yoshida J. Yamada, Zachary A. Kohutek, Simon N. Powell, Jillian Tsai, Jonathan T. Yang
Journal: Journal of Clinical Oncology (2023)

External-beam radiation therapy (RT) is standard of care (SOC) for pain relief of symptomatic bone metastases. We aimed to evaluate the efficacy of radiation to asymptomatic bone metastases in preventing skeletal-related events (SRE).In a multicenter randomized controlled trial, adult patients with widely metastatic solid tumor malignancies were stratified by histology and planned SOC (systemic therapy or observation) and randomly assigned in a 1:1 ratio to receive RT to asymptomatic high-risk bone metastases or SOC alone. The primary outcome of the trial was SRE. Secondary outcomes included hospitalizations for SRE and overall survival (OS).A total of 78 patients with 122 high-risk bone metastases were enrolled between May 8, 2018, and August 9, 2021, at three institutions across an affiliated cancer network in the United States. Seventy-three patients were evaluable for the primary end point. The most common primary cancer types were lung (27%), breast (24%), and prostate (22%). At 1 year, SRE occurred in one of 62 bone metastases (1.6%) in the RT arm and 14 of 49 bone metastases (29%) in the SOC arm (P < .001). There were significantly fewer patients hospitalized for SRE in the RT arm compared with the SOC arm (0 v 4, P = .045). At a median follow-up of 2.5 years, OS was significantly longer in the RT arm (hazard ratio [HR], 0.49; 95% CI, 0.27 to 0.89; P = .018), which persisted on multivariable Cox regression analysis (HR, 0.46; 95% CI, 0.23 to 0.85; P = .01).Radiation delivered prophylactically to asymptomatic, high-risk bone metastases reduced SRE and hospitalizations. We also observed an improvement in OS with prophylactic radiation, although a confirmatory phase III trial is warranted.
Genetic Insights on the Relation of Vascular Risk Factors and Cervical Artery Dissection
Authors: Quentin Le Grand, Leslie Ecker Ferreira, Tiina M. Metso, Sabrina Schilling, Turgut Tatlisumak, Caspar Grond-Ginsbach, Stefan T. Engelter, Philippe Lyrer, Jennifer J. Majersik, Bradford B. Worrall, Andrew M. Southerland, Hugh S. Markus, Mark Lathrop, Vincent Thijs, Didier Leys, Philippe Amouyel, Jean Dallongeville, Martin Dichgans, Alessandro Pezzini, Anna Bersano, Muralidharan Sargurupremraj, Stéphanie Debette
Journal: Journal of the American College of Cardiology (2023)